Numerous studies have established a relationship between manganese (Mn) exposure and motor function deficits in workers who are occupationally exposed. This research suggests that Mn affects several organ systems, including the central nervous system, resulting in a variety of neurobehavioral symptoms. Animal studies indicate that inhalation of Mn may interfere with the development of the prefrontal cortex and limbic regions that modulate executive cognitive function (ECF) in humans. Human studies in adults show an association between Mn exposure and cognitive deficits and dysregulated moods and behaviors, including anxiety, irritability, emotional disturbance, and aggression. Inhalation of Mn may be particularly insidious because of the direct route of transport from the olfactory bulbs through the limbic system to the prefrontal cortex. To date, no study has examined the subclinical effects of nonoccupational ambient exposures to Mn during childhood from industrial point sources on motor, cognitive, and behavioral functions. Childhood exposure to Mn is a primary concern given the vulnerability of the developing brain. Early detection of exposure and its effects may lead to effective remedies given the greater degree of brain plasticity in the young. Thus, the proposed R21 study is designed to assess the relationship between early childhood Mn exposure and ECF, motor function, and dysregulated behavior in childhood. Children will be selected from communities at known distances from environmental Mn sources, proximate to steel mills with ambient air Mn that approaches the level of occupational exposures previously associated with motor impairment. Biological and environmental assessments will be conducted to determine individual levels of exposure. The sample will have resided in these sites since birth. Also, the study design minimizes the co-occurrence of other metals, such as lead, and the statistical analyses will further adjust for such effects. Thus, the proposed study has potential to significantly expand upon prior findings related to motor effects of Mn exposures with the addition of sensitive, specifically selected, targeted, and developmentally appropriate cognitive and behavioral measures in children. Epidemiologic surveillance of populations potentially exposed to neurotoxicants may lead to (i) public health programs to prevent widespread exposures, (ii) screening programs for early detection of neurotoxicity, and (iii) treatment of resultant subclinical neurological dysfunction before severe and more permanent disability occurs. PUBLIC HEALTH RELEVANCE: This exploratory study on environmental exposure to Mn during early childhood will begin to explore the public health significance and magnitude of Mn effects on early neurofunctional deficits in groups of exposed children. The research is likely to stimulate a future large-scale study that will yield generalizable knowledge about environmental conditions of communities associated with cognitive, academic, and behavioral deficits. As a result, public health and prevention programs that incorporate findings linking environmental exposures to neurodevelopmental impacts are likely to produce significant improvements in integrity of biological, cognitive, and behavioral functioning in children with long term implications.